The cornea is the most densely innervated tissue in humans. Peripheral corneal nerves regenerate follow injury. Our hypothesis is that VEGF is a critical determinant of corneal nerve regeneration after injury and that the signaling pathways which mediate neurogenesis are distinct from those which mediate angiogenesis. Aim A will characterize the expression of VEGF and VEGF receptors and identify the receptors which mediate VEGF-dependent neurogenesis in vitro and in vivo. Aim B will characterize effect of VEGF on the regeneration of nerves in 2 injury models, while Aim C will investigate the pathways responsible for these effects. We will analyze whether there exists a differential activation of VEGF mediated neurogenesis following different injuries. PUBLIC HEALTH RELEVANCE: Proper regeneration of corneal nerves after injury is needed to prevent the development of potentially blinding neurotrophic keratitis. This application will investigate a new role in corneal nerve regeneration for the well characterized VEGF signaling pathway in order to develop new techniques for promoting corneal repair.